Factor Xa (FXa) plays a critical role in the coagulation cascade by generation of thrombin. During focal ischemia thrombin levels increase in the brain tissue and cause neural damage. This study examined the hypothesis that administration of the FXa inhibitor, apixaban, following focal ischemic stroke may have therapeutic potential by decreasing brain thrombin activity and infarct volume. Male mice were divided into a treated groups that received different doses of apixaban (2, 20, 100 mg/kg administered I...

This study was conducted to investigate the extent of absorption in different regions of the gastrointestinal (GI) tract. The relative bioavailability of an apixaban crushed tablet was also assessed to investigate the effect of dissolution on absorption. This was an open-label, randomized, 4-period, 4-treatment crossover study with a 7-day washout period balanced for first-order residual effects in 12 healthy subjects. Subjects received a single dose of a 2.5-mg apixaban solution administered orally, released in the distal small intestine and in the ascending colon...

Atrial fibrillation (AF) is the most prevalent arrhythmia and is associated with an increased risk of ischemic stroke (IS) and systemic embolism (SE). Stroke prevention is a key element for the overall management of AF patients. The non-vitamin K antagonist oral anticoagulants (NOACs), such as dabigatran, rivaroxaban, apixaban and edoxaban, are at least as effective as warfarin in reducing IS/SE with a lower rate of major bleeding. Various analyses from the large Phase III randomized trials demonstrated different efficacy and safety of NOACs in specific subgroups of patients...

BACKGROUND: Apixaban is a non-vitamin K oral anticoagulant approved for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). Current labeling recommends dose reduction based on patient age, weight, and renal function. HYPOTHESIS: The aim of this study was to analyze adherence to current labeling instructions concerning initial apixaban dosing in clinical practice and identify factors associated with inappropriate dose reduction...

Deep vein thrombosis and pulmonary artery embolisms share pathophysiological features and are therefore collectively referred to as venous thromboembolisms (VTE). While the incidence of VTE has been increasing for years as a result of demographic changes and improved diagnostics, the morbidity and mortality are decreasing. This is particularly due to more sensitive diagnostics, improvements in risk stratification and more effective anticoagulation strategies. The aim of effective anticoagulation therapy is the avoidance of early events up to death and prevention of recurrent events...

OBJECTIVE: To conduct a systematic literature review (SLR) and network meta-analysis (NMA) of real-world studies comparing major bleeding risk among patients with non-valvular atrial fibrillation (NVAF) on direct oral anticoagulants (DOACs) or warfarin. METHODS: Systematic searches were conducted in MEDLINE and Embase for full-text articles published between January 1, 2003 and March 18, 2017. Eligible studies compared at least two of the following in a real-world setting: warfarin, apixaban, dabigatran, rivaroxaban, or edoxaban...

The significance of adding new oral anticoagulants (NOACs) to antiplatelet therapy in patients with acute coronary syndrome (ACS) is unclear. We conducted a meta-analysis to assess the safety and efficacy of adding NOACs (apixaban, rivaroxaban, and dabigatran) to single antiplatelet agent (SAP) or dual antiplatelet therapy (DAPT) in patients with ACS. Seven randomized controlled trials were selected using PubMed or MEDLINE, Scopus, and Cochrane library (inception to August 2017). The summary measure was random effects hazard ratio (HR) with 95% confidence interval (CI)...

OBJECTIVE: To determine the probability of visible hematuria with antithrombotic agents and to evaluate association of urologic etiology in antithrombotic-related hematuria. METHODS: Preferred Reporting Items in Systematic Reviews and Meta-Analyses guidelines were followed to conduct a systematic review using search engines PUBMED and SCOPUS with the terms "(hematuria) OR (haematuria) OR urinary bleeding)) AND ((anticoagulants) OR anticoagulation) OR noac) OR novel anticoagulants) OR antiplatelet) OR dabigatran) OR rivaroxaban) OR apixaban) OR warfarin) OR aspirin) OR heparin) OR dipyridamole)...

BACKGROUND: The optimal dosing of novel oral P2Y12 receptor platelet inhibitors such as prasugrel or ticagrelor is unclear and especially challenging in East Asians. We hypothesize that half-dose prasugrel and ticagrelor may be sufficient for long-term maintenance management in Korean patients with the acute coronary syndrome (ACS) compared with conventional dosages. DESIGN: HOPE-TAILOR (Half Dose of Prasugrel and Ticagrelor in Platelet Response after Acute Coronary Syndromes) is a prospective, randomized, open-label, blinded, endpoint (PROBE) single-center, clinical trial...

Essentials The evidence on how to manage life-threatening pregnancy-related pulmonary embolism (PE) is scarce. We systematically reviewed all available cases of (sub)massive PE until December 2016. Thrombolysis in such severe PE was associated with a high maternal survival (94%). The major bleeding risk was much greater in the postpartum (58%) than antepartum period (18%). SUMMARY: Background Massive pulmonary embolism (PE) during pregnancy or the postpartum period is a rare but dramatic event...

Anticoagulation is essential in patients with ST elevation myocardial infarction (STEMI) to prevent further thrombosis and to maintain patency of the infarct-related artery after reperfusion. The various anticoagulant medications available for use in patients with STEMI include unfractionated heparin (UFH), low-molecular-weight heparin, fondaparinux, and bivalirudin, a direct thrombin inhibitor. The authors review the current anticoagulation strategies for patients with STEMI undergoing primary percutaneous coronary intervention (PCI), fibrinolysis, or no reperfusion...

The initial treatment of haemodynamically stable patients with pulmonary embolism (PE) has dramatically changed since the introduction of low molecular weight heparins (LMWHs). With the recent discovery of the direct oral anticoagulant drugs (DOACs), initial treatment of PE will be simplified even further. In several large clinical trials it has been demonstrated that DOACs are not inferior to standard therapy for the initial treatment of PE, and because of their practicability they are becoming the agents of first choice...

PURPOSE: To evaluate the use of direct-acting oral anticoagulants in patients with cancer and venous thromboembolism (VTE) treated at Ochsner Medical Center with the intent of determining the efficacy and safety of these agents. METHODS: Patients were identified by a retrospective data extraction of patients treated at Ochsner Medical Center from January 1, 2013, through December 31, 2015. Patients were included for review if they were ≥18 years of age, with a confirmed diagnosis of VTE and active or history of cancer, and if they received dabigatran, apixaban, rivaroxaban, or edoxaban for at least 6 months...

Direct oral anticoagulants (DOACs) can be quantified using methods that can be performed in any clinical or research laboratory using manual or automated instrument platforms. Dabigatran etexilate, the oral direct thrombin inhibitor, can be quantified by drug-calibrated clot or chromogenic-based assays using either thrombin or ecarin as substrates. Oral direct anti-Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban, can be quantified with drug-calibrated anti-Xa kits or reagents as typically used for measuring heparins (unfractionated, low molecular weight, or pentasaccharides)...

The study of pharmacogenomics presents the possibility of individualised optimisation of drug therapy tailored to each patients' unique physiological traits. Both antiplatelet and anticoagulant drugs play a key role in the management of cardiovascular disease. Despite their importance, there is a substantial volume of literature to suggest marked person-to-person variability in their effect. Areas covered: This article reviews the data available for the genetic cause for this inter-patient variability of antiplatelet and anticoagulant drugs...

The use of direct oral anticoagulants (DOACs) was an important step forward in the management of atrial fibrillation and venous thromboembolism (VTE). The DOACs, anti-IIa for dabigatran and anti-Xa for rivaroxaban, apixaban and edoxaban, all have a rapid onset of action and a short half life. There is no need for routine hemostasis testing for treatment monitoring of a DOAC. Compared with vitamin K antagonists (VKAs), DOACs may increase the risk of gastrointestinal bleeding (relative risk 1.25). Withholding the DOAC treatment, evaluating the time of the last intake and estimating the patient's renal function are the first steps in the management of gastrointestinal bleeding...

Thrombotic diseases caused by cancer progression have been reported as one of the major causes of cancer associated morbidity and mortality along with cancer invasiveness and infectious complications. Moreover, anticoagulant therapy with heparin and heparin-like drugs, or vitamin K antagonists, or the Direct Oral Anticoagulants, is seeing an extended application in cancer patients and offers prolonged life expectancy to oncology patients for whom blood activation and thrombotic events have a variable incidence, depending on cancer type...